Knockout of MicroRNA-155 Ameliorates the Th17/Th9 Immune Response and Promotes Wound Healing.

Abstract

MiRNAs are integral for maintaining immune homeostasis and self-tolerance. In this study, qPCR analyses were performed to determine which miRNAs play an important role in wound healing. Next, an experiment in a model of wound healing was performed, and histology, mRNA expression and T-cell subpopulations in wound tissue were analyzed. The accelerated experiments were performed by local injection of either rIL-17A and/or rIL-9 after wound healing. In vitro, the differentiation of Th17/Th9 in miR-155+/+ or miR-155-/- mice was investigated, and the target genes of miR155 were analyzed. From our findings, miR-155-/- in mice promoted wound healing and weakened T cell-mediated inflammation, especially in IL-17/IL-9, and less severe skin fibrosis developed in the mice. rIL-17A and/or rIL-9 could exacerbate inflammatory injury and delay wound healing. We also demonstrated that miR-155-/- led to a defect in the differentiation of Th17/Th9 in vitro, and this effect of IL-17/IL-9 might be related to the expression of C-maf, which is a target gene of miR155. MiR-155 regulated IL-17/IL-9-related inflammation in wound healing and might be a potential therapeutic target to attenuate the inflammatory response in wound tissue and promote the closure of wound injuries.